A Flavonol Glycoside, Isolated From Roots of Panax notoginseng, Reduces Amyloid-β-Induced Neurotoxicity in Cultured Neurons: Signaling Transduction and Drug Development for Alzheimer's Disease

Article type: Research Article

Authors: Choi, Roy C.Y.^{a; 1} | Zhu, Judy T.T.^{a; 1} | Leung, K. Wing^a | Chu, Glanice K.Y.^a | Xie, Heidi Q.^a | Chen, Vicky P.^a | Zheng, Ken Y.Z.^a | Lau, David T.W.^a | Dong, Tina T.X.^a | Chow, Peter C.Y.^b | Han, Yi-Fan^b | Wang, Zheng-Tao^c | Tsim, Karl W.K.^{a; *}

Affiliations: [a] Departments of Biology and Center for Chinese Medicine, The Hong Kong University of Science and Technology, Clear Water Bay Road, Hong Kong | [b] Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hung Hom, Hong Kong | [c] Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Zhangjiang Hi-Tech Park, Shanghai, China

Correspondence: [*] Correspondence to: Dr. Karl W.K. Tsim, Department of Biology, The Hong Kong University of Science and Technology, Clear Water Bay Road, Kowloon, Hong Kong SAR, China. Tel.: +86 852 2358 7332; Fax: +86 852 2358 1559; E-mail: [email protected].

Note: [1] These authors contributed equally to this work.

Abstract: A Radix Notoginseng flavonol glycoside (RNFG), quercetin 3-O-β-D-xylopyranosyl-β-D-galactopyranoside, was isolated from roots of Panax notoginseng. Among different biological properties tested, RNFG possessed a strong activity in preventing amyloid-β (Aβ)-induced cell death. In an in vitro assay, RNFG inhibited the aggregation of Aβ in a dose-dependent manner. Moreover, application of RNFG in cultured cortical neurons, or PC12 cells, reduced the Aβ-induced cell death in time- and dose-dependent manners, with the suppression of Aβ-induced DNA fragmentation and caspase-3 activation. In cultured neurons, the pre-treatment of RNFG abolished the increase of Ca2+ mobilization triggered by Aβ. The neuroprotective properties of RNFG required a specific sugar attachment within the main chemical backbone because the flavonol backbone by itself did not show any protective effect. In memory impairment experiments using the passive avoidance task, the administration of RNFG reduced brain damage in scopolamine-treated rats. These results therefore reveal a novel function of Radix Notoginseng and its flavonol glycoside that could be very useful in developing food supplements for the prevention, or potential treatment, of Alzheimer's disease.

Keywords: Alzheimer's disease, Chinese medicine, flavonol glycoside, neuroprotection, Panax notoginseng

DOI: 10.3233/JAD-2010-1293

Journal: Journal of Alzheimer's Disease, vol. 19, no. 3, pp. 795-811, 2010